Aims of the project

By performing in silico (computerized) experiments we aim:

modeling and optimizing of the structure of mu-, delta- and kappa- opioid receptors, cannabinoid receptors and neurotensin receptors;

determining the structure of the ligand-receptor complex and the minimum free energy of binding in certain structures of receptor and ligand, and studing the method of connection in order to offer modifications to ligands;

prediction of biological activity;

development of a mathematical model for predicting the biological activity by using the results of molecular docking of new ligands and the results of in vitro tests;

studying the applicability of cloud structures and server virtualization tasks in protein folding, docking and the prediction of biological activity;

Methods and models to achieve the objectives:

“hydrophobic-hydrophilic” model;

method of homology modeling;

solving the problem of protein folding by using the following three types of combinatorial algorithms: heuristic, combinatorial-optimizational, and approximational;

determining the binding mode of the ligand and the receptor using geometrical and energetic methods;

application of ligand-based and structure-based approaches, in which: molecular analysis of the fields of protein homology modeling, docking and virtual screening of bioactive compounds, the determination and analysis of protein-ligand interactions for the 3d structure of the target biomacromolecule.

Key results:

modeling and optimization of the 3d structure of the study receptors – opioid, cannabinoid, and neurotensin;

development of a mathematical model describing the relationship between the parameters and the results of the docking of particular biological importance of in vitro assays to predict biological activity of the compounds.

determination of the quantitative relationship between the biological activity of a series of compounds and their physico-chemical properties.

Stages

First stage

Installing the necessary software packages and operating systems.

Modeling and optimizing the structure of mu-, delta-and kappa-opioid, neurotensin and cannabinoid receptors.

Determining the structure of the ligand-receptor complex and the minimum free energy of binding at the known structures of the receptor and the ligand

Create virtual modules for scientific tasks provided by the project.

Study the applicability of cloud structures and server virtualization tasks in protein folding, docking and determination of biological activity.

Study the binding mode of the ligand to the receptor in order to propose modifications to the ligands.

Creating a web portal with the possibility of publishing the results of the project.

Development of a mathematical model for predicting the biological activity using the results of the molecular docking of new ligands.

Determination of biological activity of the mu-, delta-and kappa-opioid, neurotensin and cannabinoid receptors.

Organizing webinars.

Creating an interactive platform where results and expertise of the members of the project will be promoted.

Participants

Name

Organization

Assoc. Prof. PhD Ivan Trenchev

SWU-Blagoevgrad

Prof. Nevena Pencheva

SWU-Blagoevgrad

Assist. Anton Stoilov

SWU-Blagoevgrad

Assist. Radoslav Mavrevski

SWU-Blagoevgrad

Assist. Ivan Todorin

SWU-Blagoevgrad

Prof. Nicola Yanev

IMI-BAS

Assist. Tatyana Dzimbova

IMB-BAS

Fatima Sapundzhi, PhD studnet

SWU-Blagoevgrad

Metodi Traykov, PhD studnet

SWU-Blagoevgrad

Gergana Koroleova, PhD studnet

SWU-Blagoevgrad

Specific actions of SWU “Neofit Rilski” include the provision of facilities of the center for advanced bioinformatics studies (TSSBI) for the project. Facilities of TSSBI includes seminar hall with 12 work places, computer equipment, server room equipped with 5 high computational power servers. SWU “West University” will support this project by incurring overhead costs – electricity, water, etc. TSSBI will provide high-speed connectivity to the Internet and access to the infrastructure of the university.